Secukinumab Improves Clinical Response in Plaque Psoriasis

Secukinumab therapy for moderate-to-severe plaque psoriasis is safe and associated with long-term disease control.

Secukinumab is associated with greater improvement in Psoriasis Area and Severity Index (PASI) response rates at week 12 compared with placebo in patients with moderate-to-severe plaque psoriasis, according to study findings published in Journal of Dermatological Science.

Researchers conducted a randomized, double-blind, placebo-controlled, phase 4 ObePso-S trial that evaluated the efficacy and safety of secukinumab and the modulation of skin inflammation in moderate-to-severe plaque psoriasis from April 2017 to February 2019.

Participants were randomly assigned in a 2:1 ratio to receive either secukinumab or placebo for 12 weeks. Secukinumab dosing was 300 mg subcutaneously at weeks 0 through 4 and every 4 weeks afterward. Those who received placebo also received matching subcutaneous placebo injections. All participants were re-inducted in a blinded fashion after the placebo-controlled phase and assigned to receive secukinumab every 4 weeks, and randomization was stratified by weight (<90 or ≥90 kg).

The primary binary efficacy variables were a reduction of at least 90% in PASI (PASI90) and no keratin 16 (K16) expression. The primary analysis time point was week 12, and the secondary analysis time point was week 52.

[E]arly reversal of histologic and transcriptional changes associated with treatment of psoriasis with secukinumab was associated with long-term successful disease control…

A total of 82 participants received secukinumab (n=54; mean age, 41.5 [SD, 15.2] years; 59.3% men) or placebo (n=28; mean age, 50.4 [SD, 13.1] years; 71.4% men).

At week 12, a total of 29 participants (55.8%) who were treated with secukinumab achieved PASI90 vs 0 participants who received placebo (difference, 55.8%; 95% CI, 42.3%, 69.3%). At week 52, 31 participants (59.6%) in the initial secukinumab group and 20 (71.4%) in the initial placebo group achieved PASI90.

Biopsy evaluation at week 12 demonstrated that 79.6% of participants who received secukinumab had no detectable K16 expression vs 3.6% of those who received placebo (difference, 76.1%; 95% CI, 63.3%, 88.8%). At week 52, normalization of K16 occurred in most participants in the 2 groups. There was an absence of K16 staining in 93.1% and 93.6% of week 12 and week 52 PASI90 responders, respectively. The rate of PASI90 response at week 12 in the secukinumab subgroups (60.0% of <90-kg subgroup vs 51.9% of ≥90-kg subgroup).

The proportions of participants in the secukinumab group who achieved Investigator Global Assessment modified 2011 score of 0 out of 1 were 75.6% at week 12 and 72.7% at week 52.

Among participants who achieved PASI90 at week 52, those who received secukinumab had 95% improvement in genes initially up-regulated in the baseline transcriptome and 87% improvement in down-regulated genes at week 12. At week 52, the up- and down-regulated transcripts improved by approximately 85% to 87% for responders. In week 12 biopsies, nonresponders had lower molecular improvements (75%-84% improvement), and this response decreased to 40% to 43% in week 52 biopsies.

In the secukinumab group, week 12 transcriptome improvements were greater among week 52 clinical responders vs week 52 nonresponders. In week 12 biopsies, changes in expression of some genes were highly associated with PASI outcomes at week 52. Improvements in PASI were highly correlated at week 52 with mean changes in vanin 2 (r, -0.71; 95% CI, -0.86 to -0.44; P <.001) and interleukin-6 (r, -0.72; 95% CI, -0.87 to -0.45; P <.001) expression at week 12.

“[E]arly reversal of histologic and transcriptional changes associated with treatment of psoriasis with secukinumab was associated with long-term successful disease control and confirmed the known clinical response and safety of secukinumab in patients with moderate-to-severe psoriasis,” the researchers concluded.

Disclosure: This study was sponsored by Novartis Pharmaceuticals Corporation. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Blauvelt A, Pariser DM, Tyring S, et al. Psoriasis improvements and inflammatory biomarker normalization with secukinumab: the randomized ObePso-S study. J Dermatol Sci. Published online January 9, 2023. doi:10.1016/j.jdermsci.2023.01.003